1. Immune system has two intrinsic systems
Immunity
Resistance to disease
Immune system has two intrinsic systems
Innate (nonspecific) defense system
Adaptive (specific) defense system

2. Innate defense system has two lines of defense
Immunity
Innate defense system has two lines of defense
First line of defense is external body membranes (skin and mucosae)
Second line of defense is antimicrobial proteins, phagocytes, and other cells
Inhibit spread of invaders
Inflammation is its most important mechanism

3. Adaptive defense system
Immunity
Adaptive defense system
Third line of defense attacks particular foreign substances
Takes longer to react than the innate system
Innate and adaptive defenses are deeply intertwined

4. • Antimicrobial proteins • Fever
Surface barriers
• Skin
• Mucous membranes
Innate
defenses
Internal defenses
• Phagocytes
• NK cells
• Inflammation
• Antimicrobial proteins
• Fever
Humoral immunity
• B cells
Adaptive
defenses
Cellular immunity
• T cells
Figure 21.1

5. Innate Defenses Surface barriers
Skin, mucous membranes, and their secretions
Physical barrier to most microorganisms
Keratin is resistant to weak acids and bases, bacterial enzymes, and toxins
Mucosae provide similar mechanical barriers

6. Protective chemicals inhibit or destroy microorganisms
Surface Barriers
Protective chemicals inhibit or destroy microorganisms
Skin acidity
Lipids in sebum and dermcidin in sweat
HCl and protein-digesting enzymes of stomach mucosae
Lysozyme of saliva and lacrimal fluid
Mucus

7. Respiratory system modifications
Surface Barriers
Respiratory system modifications
Mucus-coated hairs in the nose
Cilia of upper respiratory tract sweep dust- and bacteria-laden mucus from lower respiratory passages

8. Internal Defenses: Cells and Chemicals
Necessary if microorganisms invade deeper tissues
Phagocytes
Natural killer (NK) cells
Inflammatory response (macrophages, mast cells, WBCs, and inflammatory chemicals)
Antimicrobial proteins (interferons and complement proteins)
Fever

9. Phagocytes: Macrophages
Macrophages develop from monocytes to become the chief phagocytic cells
Free macrophages wander through tissue spaces
E.g., alveolar macrophages
Fixed macrophages are permanent residents of some organs
E.g., Kupffer cells (liver) and microglia (brain)

10. Phagocytes: Neutrophils
Become phagocytic on encountering infectious material in tissues

11. Mechanism of Phagocytosis
Step 1: Adherence of phagocyte to pathogen
Facilitated by opsonization—coating of pathogen by complement proteins or antibodies

12. Innate defenses Internal defenses
(a) A macrophage (purple) uses its cytoplasmic extensions to pull spherical bacteria (green) toward it. Scanning electron micrograph (1750x).
Figure 21.2a

13. (b) Events of phagocytosis.
Phagocyte
adheres to
pathogens or debris. 1
Phagocyte forms
pseudopods that
eventually engulf the
particles forming a
phagosome. 2
Phagosome
(phagocytic
vesicle)
Lysosome
Lysosome fuses
with the phagocytic
vesicle, forming a
phagolysosome. 3
Acid
hydrolase
enzymes
Lysosomal
enzymes digest the
particles, leaving a
residual body. 4
Exocytosis of the
vesicle removes
indigestible and
residual material. 5
(b) Events of phagocytosis.
Figure 21.2b

14. Mechanism of Phagocytosis
Destruction of pathogens
Acidification and digestion by lysosomal enzymes
Respiratory burst
Release of cell-killing free radicals
Activation of additional enzymes
Oxidizing chemicals (e.g. H2O2)
Defensins (in neutrophils)

15. Natural Killer (NK) Cells
Large granular lymphocytes
Target cells that lack “self” cell-surface receptors
Induce apoptosis in cancer cells and virus-infected cells
Secrete potent chemicals that enhance the inflammatory response

16. Inflammatory Response
Triggered whenever body tissues are injured or infected
Prevents the spread of damaging agents
Disposes of cell debris and pathogens
Sets the stage for repair

17. Inflammatory Response
Cardinal signs of acute inflammation:
Redness
Heat
Swelling
Pain
(And sometimes 5. Impairment of function)

18. Inflammatory Response
Macrophages and epithelial cells of boundary tissues bear Toll-like receptors (TLRs)
TLRs recognize specific classes of infecting microbes
Activated TLRs trigger the release of cytokines that promote inflammation

19. Inflammatory Response
Inflammatory mediators
Histamine (from mast cells)
Blood proteins
Kinins, prostaglandins (PGs), leukotrienes, and complement
Released by injured tissue, phagocytes, lymphocytes, basophils, and mast cells

20. Vasodilation and Increased Vascular Permeability
Inflammatory chemicals cause
Dilation of arterioles, resulting in hyperemia
Increased permeability of local capillaries and edema (leakage of exudate)
Exudate contains proteins, clotting factors, and antibodies

21. Inflammatory Response: Edema
Functions of the surge of exudate
Moves foreign material into lymphatic vessels
Delivers clotting proteins to form a scaffold for repair and to isolate the area

22. Figure 21.3 Innate defenses Internal defenses Tissue injury
Release of chemical mediators
(histamine, complement,
kinins, prostaglandins, etc.)
Release of leukocytosis-
inducing factor
Leukocytosis
(increased numbers of white
blood cells in bloodstream)
Vasodilation
of arterioles
Increased capillary
permeability
Attract neutrophils,
monocytes, and
lymphocytes to
area (chemotaxis)
Leukocytes migrate to
injured area
Local hyperemia
(increased blood
flow to area)
Capillaries
leak fluid
(exudate formation)
Margination
(leukocytes cling to
capillary walls)
Initial stimulus
Physiological response
Signs of inflammation
Diapedesis
(leukocytes pass through
capillary walls)
Leaked protein-rich
fluid in tissue spaces
Leaked clotting
proteins form interstitial
clots that wall off area
to prevent injury to
surrounding tissue
Result
Phagocytosis of pathogens
and dead tissue cells
(by neutrophils, short-term;
by macrophages, long-term)
Heat
Redness
Pain
Swelling
Locally increased
temperature increases
metabolic rate of cells
Possible temporary
limitation of
joint movement
Temporary fibrin
patch forms
scaffolding for repair
Pus may form
Area cleared of debris
Healing
Figure 21.3

23. Phagocyte Mobilization
Neutrophils, then phagocytes flood to inflamed sites

24. Phagocyte Mobilization
Steps for phagocyte mobilization
Leukocytosis: release of neutrophils from bone marrow in response to leukocytosis-inducing factors from injured cells
Margination: neutrophils cling to the walls of capillaries in the inflamed area
Diapedesis of neutrophils
Chemotaxis: inflammatory chemicals (chemotactic agent) promote positive chemotaxis of neutrophils

25. Chemotaxis. Neutrophils follow chemical trail.
Innate defenses
Internal defenses
Inflammatory chemicals diffusing from the inflamed site act as chemotactic agents.
Chemotaxis. Neutrophils follow chemical trail. 4
Capillary wall
Basement membrane
Endothelium 1
Leukocytosis. Neutrophils enter blood from bone marrow. 2
Margination. Neutrophils cling to capillary wall.
Diapedesis. Neutrophils flatten and squeeze out of capillaries. 3
Figure 21.4

26. Leukocytosis. Neutrophils enter blood from bone marrow.
Innate defenses
Internal defenses
Inflammatory chemicals diffusing from the inflamed site act as chemotactic agents.
Capillary wall
Basement membrane
Endothelium 1
Leukocytosis. Neutrophils enter blood from bone marrow.
Figure 21.4, step 1

27. Leukocytosis. Neutrophils enter blood from bone marrow.
Innate defenses
Internal defenses
Inflammatory chemicals diffusing from the inflamed site act as chemotactic agents.
Capillary wall
Basement membrane
Endothelium 1
Leukocytosis. Neutrophils enter blood from bone marrow. 2
Margination. Neutrophils cling to capillary wall.
Figure 21.4, step 2

28. Leukocytosis. Neutrophils enter blood from bone marrow.
Innate defenses
Internal defenses
Inflammatory chemicals diffusing from the inflamed site act as chemotactic agents.
Capillary wall
Basement membrane
Endothelium 1
Leukocytosis. Neutrophils enter blood from bone marrow. 2
Margination. Neutrophils cling to capillary wall. 3
Diapedesis. Neutrophils flatten and squeeze out of capillaries.
Figure 21.4, step 3

29. Chemotaxis. Neutrophils follow chemical trail.
Innate defenses
Internal defenses
Inflammatory chemicals diffusing from the inflamed site act as chemotactic agents.
Chemotaxis. Neutrophils follow chemical trail. 4
Capillary wall
Basement membrane
Endothelium 1
Leukocytosis. Neutrophils enter blood from bone marrow. 2
Margination. Neutrophils cling to capillary wall.
Diapedesis. Neutrophils flatten and squeeze out of capillaries. 3
Figure 21.4, step 4

30. Antimicrobial Proteins
Interferons (IFNs) and complement proteins
Attack microorganisms directly
Hinder microorganisms’ ability to reproduce

31. Interferons
Viral-infected cells are activated to secrete IFNs
IFNs enter neighboring cells
Neighboring cells produce antiviral proteins that block viral reproduction

32. Antiviral proteins block viral reproduction.
Innate defenses
Internal defenses
Virus 1
Virus enters cell.
New viruses
Viral nucleic acid
Antiviral proteins block viral reproduction. 5 2
Interferon genes switch on.
DNA
Nucleus
mRNA 4
Interferon binding stimulates cell to turn on genes for antiviral proteins. 3
Cell produces interferon molecules.
Interferon
Host cell 2 Binds interferon from cell 1; interferon induces synthesis of protective proteins
Host cell 1 Infected by virus; makes interferon; is killed by virus
Figure 21.5

33. Host cell 1 Infected by virus; makes interferon; is killed by virus
Innate defenses
Internal defenses
Virus
Virus enters cell. 1
Viral nucleic acid
Nucleus
Host cell 2 Binds interferon from cell 1; interferon induces synthesis of protective proteins
Host cell 1 Infected by virus; makes interferon; is killed by virus
Figure 21.5, step 1

34. Interferon genes switch on.
Innate defenses
Internal defenses
Virus 1
Virus enters cell.
Viral nucleic acid 2
Interferon genes switch on.
DNA
Nucleus
Host cell 2 Binds interferon from cell 1; interferon induces synthesis of protective proteins
Host cell 1 Infected by virus; makes interferon; is killed by virus
Figure 21.5, step 2

35. Interferon genes switch on.
Innate defenses
Internal defenses
Virus 1
Virus enters cell.
Viral nucleic acid 2
Interferon genes switch on.
DNA
Nucleus
mRNA 3
Cell produces interferon molecules.
Interferon
Host cell 2 Binds interferon from cell 1; interferon induces synthesis of protective proteins
Host cell 1 Infected by virus; makes interferon; is killed by virus
Figure 21.5, step 3

36. Interferon genes switch on.
Innate defenses
Internal defenses
Virus 1
Virus enters cell.
Viral nucleic acid
Interferon genes switch on. 2
DNA
Nucleus
mRNA 4
Interferon binding stimulates cell to turn on genes for antiviral proteins. 3
Cell produces interferon molecules.
Interferon
Host cell 2 Binds interferon from cell 1; interferon induces synthesis of protective proteins
Host cell 1 Infected by virus; makes interferon; is killed by virus
Figure 21.5, step 4

37. Antiviral proteins block viral reproduction.
Innate defenses
Internal defenses
Virus 1
Virus enters cell.
New viruses
Viral nucleic acid
Antiviral proteins block viral reproduction. 5 2
Interferon genes switch on.
DNA
Nucleus
mRNA 4
Interferon binding stimulates cell to turn on genes for antiviral proteins. 3
Cell produces interferon molecules.
Interferon
Host cell 2 Binds interferon from cell 1; interferon induces synthesis of protective proteins
Host cell 1 Infected by virus; makes interferon; is killed by virus
Figure 21.5, step 5

38. Produced by a variety of body cells
Interferons
Produced by a variety of body cells
Lymphocytes produce gamma (), or immune, interferon
Most other WBCs produce alpha () interferon
Fibroblasts produce beta () interferon
Interferons also activate macrophages and mobilize NKs

39. Genetically engineered IFNs for
Interferons
Functions
Anti-viral
Reduce inflammation
Activate macrophages and mobilize NK cells
Genetically engineered IFNs for
Antiviral agents against hepatitis and genital warts virus
Multiple sclerosis treatment

40. Complement
~20 blood proteins that circulate in an inactive form
Include C1–C9, factors B, D, and P, and regulatory proteins
Major mechanism for destroying foreign substances

41. Complement
Amplifies all aspects of the inflammatory response
Kills bacteria and certain other cell types by cell lysis
Enhances both nonspecific and specific defenses

42. Complement Activation
Two pathways
Classical pathway
Antibodies bind to invading organisms
C1 binds to the antigen-antibody complexes (complement fixation)
Alternative pathway
Triggered when activated C3, B, D, and P interact on the surface of microorganisms

43. Complement Activation
Each pathway involves activation of proteins in an orderly sequence
Each step catalyzes the next
Both pathways converge on C3, which cleaves into C3a and C3b

44. Complement Activation
Activated complement
Enhances inflammation
Promotes phagocytosis
Causes cell lysis
C3b initiates formation of a membrane attack complex (MAC)
MAC causes cell lysis by inducing a massive influx of water
C3b also causes opsonization, and C3a causes inflammation

45. Antigen-antibody complex Spontaneous activation + +
Classical pathway
Alternative pathway
Antigen-antibody complex
Spontaneous activation + +
Stabilizing factors (B, D, and P) +
complex
No inhibitors on pathogen
surface
Opsonization:
Enhances inflammation:
coats pathogen
surfaces, which
enhances phagocytosis
stimulates histamine release,
increases blood vessel
permeability, attracts
phagocytes by chemotaxis,
etc.
Insertion of MAC and cell lysis
(holes in target cell’s membrane)
Pore
Complement
proteins
(C5b–C9)
Membrane
of target cell
Figure 21.6

46. Fever
Systemic response to invading microorganisms
Leukocytes and macrophages exposed to foreign substances secrete pyrogens
Pyrogens reset the body’s thermostat upward

47. High fevers are dangerous because heat denatures enzymes
Benefits of moderate fever
Causes the liver and spleen to sequester iron and zinc (needed by microorganisms)
Increases metabolic rate, which speeds up repair

48. The adaptive immune (specific defense) system
Adaptive Defenses
The adaptive immune (specific defense) system
Protects against infectious agents and abnormal body cells
Amplifies the inflammatory response
Activates complement

49. Adaptive immune response
Adaptive Defenses
Adaptive immune response
Is specific
Is systemic
Has memory
Two separate overlapping arms
Humoral (antibody-mediated) immunity
Cellular (cell-mediated) immunity

50. Antigens
Substances that can mobilize the adaptive defenses and provoke an immune response
Most are large, complex molecules not normally found in the body (nonself)

51. Important functional properties
Complete Antigens
Important functional properties
Immunogenicity: ability to stimulate proliferation of specific lymphocytes and antibodies
Reactivity: ability to react with products of activated lymphocytes and antibodies released
Examples: foreign protein, polysaccharides, lipids, and nucleic acids

52. Haptens (Incomplete Antigens)
Small molecules (peptides, nucleotides, and hormones)
Not immunogenic by themselves
Are immunogenic when attached to body proteins
Cause the immune system to mount a harmful attack
Examples: poison ivy, animal dander, detergents, and cosmetics

53. Antigenic Determinants
Certain parts of an entire antigen that are immunogenic
Antibodies and lymphocyte receptors bind to them

54. Antigenic Determinants
Most naturally occurring antigens have numerous antigenic determinants that
Mobilize several different lymphocyte populations
Form different kinds of antibodies against it
Large, chemically simple molecules (e.g., plastics) have little or no immunogenicity

55. Antigenic determinants
binding
sites
Antigenic determinants
Antibody A
Antigen
Antibody B
Antibody C
Figure 21.7

56. Self-Antigens: MHC Proteins
Protein molecules (self-antigens) on the surface of cells
Antigenic to others in transfusions or grafts
Example: MHC proteins
Coded for by genes of the major histocompatibility complex (MHC) and are unique to an individual

57. MHC Proteins Classes of MHC proteins
Class I MHC proteins, found on virtually all body cells
Class II MHC proteins, found on certain cells in the immune response
MHC proteins display peptides (usually self-antigens)
In infected cells, MHC proteins display fragments of foreign antigens, which help mobilize

58. Cells of the Adaptive Immune System
Two types of lymphocytes
B lymphocytes (B cells)—humoral immunity
T lymphocytes (T cells)—cell-mediated immunity
Antigen-presenting cells (APCs)
Do not respond to specific antigens
Play essential auxiliary roles in immunity

59. Originate in red bone marrow
Lymphocytes
Originate in red bone marrow
B cells mature in the red bone marrow
T cells mature in the thymus

60. Lymphocytes When mature, they have
Immunocompetence; they are able to recognize and bind to a specific antigen
Self-tolerance – unresponsive to self antigens
Naive (unexposed) B and T cells are exported to lymph nodes, spleen, and other lymphoid organs

61. Lymphocytes destined to become T cells
Humoral immunity
Red bone marrow: site of lymphocyte origin
Adaptive defenses
Cellular immunity
Primary lymphoid organs: site of
development of immunocompetence as B or
T cells
Immature
lymphocytes
Red
bone marrow
Secondary lymphoid organs: site of
antigen encounter, and activation to become
effector and memory B or T cells
Lymphocytes destined to become T cells
migrate (in blood) to the thymus and develop
immunocompetence there. B cells develop
immunocompetence in red bone marrow. 1
Thymus
Bone marrow
Immunocompetent but still naive
lymphocytes leave the thymus and bone
marrow. They “seed” the lymph nodes,
spleen, and other lymphoid tissues where
they encounter their antigen. 2
Lymph nodes,
spleen, and other
lymphoid tissues
Antigen-activated immunocompetent
lymphocytes (effector cells and memory
cells) circulate continuously in the
bloodstream and lymph and throughout
the lymphoid organs of the body. 3
Figure 21.8

62. T Cells
T cells mature in the thymus under negative and positive selection pressures
Positive selection
Selects T cells capable of binding to self-MHC proteins (MHC restriction)
Negative selection
Prompts apoptosis of T cells that bind to self-antigens displayed by self-MHC
Ensures self-tolerance

63. Positive selection: T cells must recognize self major
Adaptive defenses
Positive selection: T cells must recognize self major
histocompatibility proteins (self-MHC).
Antigen-
presenting
thymic cell
Failure to recognize self-MHC
results in apoptosis (death
by cell suicide).
Recognizing self-MHC results in
MHC restriction—survivors are
restricted to recognizing antigen
on self-MHC. Survivors proceed
to negative selection.
Recognizing self-antigen results
in apoptosis. This eliminates
self-reactive T cells that could
cause autoimmune diseases.
Failure to recognize (bind tightly
to) self-antigen results in survival
and continued maturation.
MHC
Self-antigen
T cell receptor
Developing
T cell
Cellular immunity
Negative selection: T cells must not recognize self-antigens.
Figure 21.9

64. B cells mature in red bone marrow Self-reactive B cells
Are eliminated by apoptosis (clonal deletion) or
Undergo receptor editing – rearrangement of their receptors
Are inactivated (anergy) if they escape from the bone marrow

65. Antigen Receptor Diversity
Lymphocytes make up to a billion different types of antigen receptors
Coded for by ~25,000 genes
Gene segments are shuffled by somatic recombination
Genes determine which foreign substances the immune system will recognize and resist

66. Antigen-Presenting Cells (APCs)
Engulf antigens
Present fragments of antigens to be recognized by T cells
Major types
Dendritic cells in connective tissues and epidermis
Macrophages in connective tissues and lymphoid organs
B cells

67. Figure 21.10

68. Macrophages and Dendritic Cells
Present antigens and activate T cells
Macrophages mostly remain fixed in the lymphoid organs
Dendritic cells internalize pathogens and enter lymphatics to present the antigens to T cells in lymphoid organs
Activated T cells release chemicals that
Prod macrophages to become insatiable phagocytes and to secrete bactericidal chemicals

69. Adaptive Immunity: Summary
Uses lymphocytes, APCs, and specific molecules to identify and destroy nonself substances
Depends upon the ability of its cells to
Recognize antigens by binding to them
Communicate with one another so that the whole system mounts a specific response

70. Humoral Immunity Response
Antigen challenge
First encounter between an antigen and a naive immunocompetent lymphocyte
Usually occurs in the spleen or a lymph node
If the lymphocyte is a B cell
The antigen provokes a humoral immune response
Antibodies are produced

71. Clonal Selection
B cell is activated when antigens bind to its surface receptors and cross-link them
Receptor-mediated endocytosis of cross-linked antigen-receptor complexes occurs
Stimulated B cell grows to form a clone of identical cells bearing the same antigen-specific receptors (T cells are usually required to help B cells achieve full activation)

72. Most clone cells become plasma cells
Fate of the Clones
Most clone cells become plasma cells
secrete specific antibodies at the rate of 2000 molecules per second for four to five days

73. Fate of the Clones Secreted antibodies Circulate in blood or lymph
Bind to free antigens
Mark the antigens for destruction

74. Clone cells that do not become plasma cells become memory cells
Fate of the Clones
Clone cells that do not become plasma cells become memory cells
Provide immunological memory
Mount an immediate response to future exposures of the same antigen

75. Adaptive defenses Humoral immunity Primary response (initial encounter
with antigen)
Antigen
Antigen binding
to a receptor on a
specific B lymphocyte
(B lymphocytes with
non-complementary
receptors remain
inactive)
Proliferation to
form a clone
Activated B cells
Plasma cells
(effector B cells)
Memory B cell—
primed to
respond to same
antigen
Secreted
antibody
molecules
Figure (1 of 2)